1. Field of the Invention
This invention relates to a measuring device for a liquid sample and a method for measuring the liquid sample, where a sensor comprising an enzyme layer is used to determine a particular component contained in a liquid sample introduced from a liquid sample inlet channel.
2. Description of the Prior Art
For measuring a component in a liquid sample such as blood and case fluid, there has been widely employed an approach that a collected liquid sample such as blood and case fluid is directly introduced into a sensor unit, it is measured with the sensor and then the liquid sample is discharged. In such a measuring procedure, a particular component is measured during the liquid sample as a continuous flow passes over the sensor surface.
JP-A 10-339716 has disclosed an example of such a measuring device for a liquid sample. FIG. 10 shows the structure of the device. This device consists of a case 48, a sensor platform 47, a measuring circuit 61, a data processor 62 and a data display 63. The case 48 comprises a standard liquid inlet 41, a standard liquid outlet 42, a sample inlet 44 and a sample outlet 43. The sensor platform 47 consists of a screw 45, a stopper 49, a sensor 46, and two liquid inlet channels 50a and 50b. The stopper 49 and the sensor 46 are fixed on the platform 47 with the screw 45. A signal detected by the sensor 46 is transmitted via an electric cable 53 through the measuring circuit 61, the data processor 62 and finally to the data display 62 where the signal is displayed as a measured value. The sensor platform 47 and the case 48 are placed in a manner that they are mutually slidable.
The sensor 46 in the liquid inlet channels 50a and 50b is removably fixed inside of the liquid inlet channel 50a by the sensor platform 47. Here, the sensor is fixed such that the exposed surface of the sensor 46 to the liquid inlet channel 50a is placed in the substantially same plane as, preferably slightly inner than, the inner surface of the liquid inlet channel 50a. Thus, in the liquid inlet channel 50a, a standard or sample liquid may not be disturbed or remain and therefore may be quickly charged and discharged.
The above prior art have advantages that a small amount of liquid sample may be measured and that since a sensor unit is removable, a worn sensor may be replaced with a new one. Furthermore, despite a simple structure, such a device may achieve good measurement accuracy. However, a measuring device with a simple structure has been recently required to achieve performance comparable to a larger device, and there is a room for improving measurement accuracy and stability in a measured value.
In a device measuring a liquid sample by introducing it to a sensor unit via a channel, particularly a device measuring a liquid sample as a continuous flow during it passes over the sensor surface, the sensor is generally placed on the side wall of the channel so that the liquid sample flows in parallel to a plane containing the sensor surface. The above-mentioned application has disclosed an example of a device having such a configuration.
However, when a sensor has an enzyme layer in the upper part of its electrode in a device having such a configuration, it may cause reduced measurement accuracy, unstable measured value and reduced response.
In a sensor comprising an enzyme layer, a component to be measured is diffused in the enzyme layer and is subject to an enzyme reaction in the enzyme layer to generate a current in an electrode which gives a measured value. In such a sensor, the amount of a chemical species derived from the component to be measured which reaches the electrode depends on a concentration of the component to be measured near the sensor surface. However, when the liquid sample moves to a direction parallel to the sensor surface, the concentration of the component to be measured may tend to vary near the sensor surface, leading to reduced measurement accuracy and unstable measured value.
When placing the sensor on the side wall of the channel, it is difficult to place the sensor such that its surface is in the completely same plane as that of the inner wall of the channel. Resultantly, a slight misalignment may lead to protrusion or depression of the sensor surface. Such a shape may cause disturbance of liquid sample flow near the sensor surface where the concentration of the component to be measured may, thus, vary, leading to reduced measurement accuracy and unstable measured value. Furthermore, in a second measurement after the first measurement and washing, a dead space which may be formed near the sensor may frequently cause reduced measurement accuracy, unstable measured value and reduced response due to residual measured liquid sample or washing. In particular, when using a biological fluid as a liquid sample, the amount of the sample is so small that a dead space formed may give significant influence. In this respect, the above-mentioned JP-A 10-339716 has descried that protrusion or depression of a sensor surface may reduce measurement sensitivity.
In addition, in a measuring device where a sensor is removable from its installation site, its structure may cause misalignment of the sensor surface to the inner wall of the channel. Furthermore, whenever replacing a sensor, precise alignment is required so that sensor replacement becomes difficult work. Thus, problems due to misalignment between the inner wall of the channel and the sensor surface becomes more prominent for a measuring device in which a sensor is removable.
On the other hand, for example, the inner structure of the channel may be improved for solving the above problems. However, such an improvement may lead to a complex device structure, thus make sensor replacement difficult and make mass production or cost reduction of the device difficult.
In addition, in a measuring device according to the prior art, a measured value may become unstable when measuring a biological fluid as a liquid sample repeatedly or continuously, which may be due to adhesion of contaminants such as proteins contained in the biological fluid on the inner wall of the channel. In a measuring device according to the prior art, there is also a room for improvement in this respect.
In view of the above problems, an object of this invention is to provide a device with an enzyme layer for measuring a liquid sample and a method for measuring the liquid sample, which may achieve excellent measurement accuracy, stable measurement sensitivity and quick response as well as prevention of sensitivity reduction in repeated or continuous measurement. In particular, an objective of this invention is to solve the above problems in a measuring device in which a sensor unit is removable.
This invention provides a device for measuring a liquid sample comprising:
a sensor for measuring a component in the liquid sample;
a liquid sample inlet channel for feeding the liquid sample to the sensor surface; and
a liquid sample outlet channel for discharging the liquid sample from the sensor surface,
the sensor having an electrode and an enzyme layer in the upper part of the electrode,
the liquid sample inlet channel being placed at an angle to the sensor surface, and one opening end of the liquid sample inlet channel being placed in the vicinity of the sensor surface.
As described above, in a conventional measuring device generally having a style that a sensor is mounted on the side wall of a channel, there has been problems of, for example, reduced measurement accuracy, unstable measured value and reduced response when using a sensor comprising an enzyme layer. To solve the problem, this invention employs a configuration that a liquid sample inlet channel is placed at an angle to a sensor surface and one opening end of the liquid sample inlet channel is placed in the vicinity of the sensor surface, whereby a flow condition of the liquid sample suitable to measurement near the sensor surface may be achieved, resulting in excellent measurement accuracy, stable measurement sensitivity and quick response. Even when the liquid sample inlet channel is placed at an angle to the sensor surface, if one opening end of the liquid sample inlet channel is too distant from the sensor surface, the above effect may not be adequately achieved because the flow condition of the liquid sample is not necessarily good near the sensor surface. In this invention, the distance between the opening end and the sensor surface is, for example, two fold or less of the inner diameter of the liquid sample inlet channel, preferably equal to or less than the inner diameter of the liquid sample inlet channel.
In this invention, a configuration where the liquid sample inlet channel is placed at an angle to the sensor surface may further improve the flow condition near the sensor surface to significantly improve measurement accuracy and measured-value stability.
This invention also provides a device for measuring a liquid sample comprising a sensor for measuring a component in the liquid sample and an upper and a lower cases vertically sandwiching the sensor, where the upper case comprises a liquid sample inlet channel for feeding the liquid sample to the sensor surface and a liquid sample outlet channel for discharging the liquid sample from the sensor surface, the sensor comprising an electrode and an enzyme layer in the upper part of the electrode and being removable from the upper case, the liquid sample inlet channel being placed at an angle to the sensor surface and one opening end of the liquid sample inlet channel being placed in the vicinity of the sensor surface.
In the device of this invention, since the sensor is removable from the upper case, a worn sensor may be quickly replaced. Furthermore, the inside of the device may be cleaned after removing the sensor. Since the sensor, the upper case and the lower case may be separately manufactured, the upper and the lower cases may be produced from a plastic material in a large scale by, for example, injection molding and degree of freedom may be increased in designing a shape of the sensor. For example, a layout of the electrode in the sensor may be freely changed.
In a measuring device in which a sensor is removable from an upper case, a sensor surface may be generally misaligned to the inner wall of a liquid sample inlet or outlet channel (hereinafter, referred to as a xe2x80x9cchannelxe2x80x9d as appropriate). Furthermore, whenever replacing a sensor, precise alignment is required, leading to reduced workability. Since removing a worn sensor and mounting a new sensor are usually conducted manually by a user of the measuring device on site, controlling the problem is an important technical subject.
To solve the problem, in this invention the liquid sample inlet channel is placed at an angle to the sensor surface while one opening end of the liquid sample inlet channel is placed in the vicinity of the sensor surface, so that a flow state near the sensor surface becomes suitable to measurement and influence of misalignment may be relatively reduced. Small misalignment of the sensor may, therefore, cause the minimum reduction in measurement accuracy and measured-value stability.
As described above, since the liquid sample measuring device according to this invention has a removable sensor unit, it may not only provide a variety of advantages but also effectively resolve the problem prominently caused when employing the above configuration, i.e., misalignment of the sensor surface to the inner wall of the channel.
Additionally, the above device for measuring a liquid sample may have a configuration that an elastic member having an opening is placed between the upper case and the sensor surface; the opening interconnects between the liquid sample inlet channel and the sensor, and between the liquid sample outlet channel and the sensor; and a part of the sensor surface is in contact with the liquid sample via the opening. Such a configuration may provide the following effects.
First, it may prevent a dead space from being formed between the upper case and the sensor, leading to good measurement accuracy, stable measured value and good response. Adequate measurement accuracy may be achieved even with a small amount of sample.
When a case with a channel is directly in contact with the sensor surface, it may often cause a gap between the case and the sensor surface. Such a gap may disturb the flow condition of the liquid sample over the sensor surface, leading to reduced measurement accuracy, unstable measured value and reduced response. Although an adhesive may be used to prevent such a gap, it may integrate the sensor with the case and therefore, a configuration with a removable sensor unit may not be provided. On the other hand, in this invention, an elastic member is placed between the sensor and the upper case. The elastic member having proper elasticity can prevent a gap from being formed between the upper case and the sensor and therefore may prevent disturbance of the flow condition of the liquid sample over the sensor surface. Consequently, a good flow condition of the liquid sample may be achieved, resulting in good measurement accuracy, stable measured value and good response.
Second, it may prevent leakage between the upper case and the sensor. As described above, the elastic member in this invention has proper elasticity so that it may prevent a gap between the upper case and the sensor, resulting in effective prevention of leakage of the liquid sample.
Third, it may significantly reduce effects of misalignment during mounting the sensor on the case.
In this invention, a part of the sensor surface is in contact with a liquid sample via an opening. Specifically, the opening defines a part of the sensor surface to be in contact with the liquid sample, and plays a role of a guide for introducing the liquid sample to a given area on the sensor surface. It may, therefore, prevent the problem that misalignment during mounting the sensor on the case causes protrusion of the sensor in the channel or that the liquid sample is in contact with the side wall of the sensor. Since the position of the sensor may be made stable to the channel, the flow condition of the liquid sample near the sensor surface becomes stable, resulting in improved measurement accuracy, measured-value stability and response.
This invention also provides a method for measuring a liquid sample wherein using a device for measuring a liquid sample comprising a sensor having an electrode and an enzyme layer in the upper part of the electrode, a liquid sample inlet channel for feeding the liquid sample to the sensor surface and a liquid sample outlet channel for discharging the liquid sample from the sensor surface, a component in the liquid sample is measured while continuously moving the liquid sample fed from the liquid sample inlet channel over the sensor surface, a moving speed of the liquid sample being adjusted to provide a sensor output in proportion to a concentration of the liquid sample.
In the method for measuring a liquid sample where a component in the liquid sample is measured while continuously moving the liquid sample over the sensor surface, measurement accuracy and measured-value stability may significantly vary depending on a moving speed of the liquid sample. Taking it into account in the method for measuring a liquid sample, a moving speed of the liquid sample is adjusted to provide accurate and stable measurement results. Specifically, the speed is adjusted to provide a sensor output in proportion to a concentration of a component to be determined. According to the method for measuring a liquid sample of this invention, employing the above adjusting procedure may provide good measurement accuracy and stable measured value.